A novel application of [Cr(en)2]2+ in the synthesis of 1,2-diols from aromatic aldehydes

Article abstract of DOI:10.1246/cl.2010.500

A reductive pinacol type arylaldehyde homocoupling process mediated by the [Cr(en)₂]²⁺ complex is described. This procedure affords the mavo-stereoisomer as the major product, an unexpected result considering that most organometallic methodologies preferentially yield the dl-isomer. Additionally, the method represents a novel application of the [Cr(en) ₂]²⁺.

Full text of DOI:10.1246/cl.2010.500

doi:10.1246/cl.2010.500
500
Published on the web April 10, 2010
A Novel Application of [Cr(en)2]2+ in the Synthesis of 1,2-Diols
from Aromatic Aldehydes
Alcives Avila-Sorrosa, Leticia Vega-Ramírez, Rafael Rodríguez-Domínguez,
Héctor Salgado-Zamora, Javier Peralta-Cruz, and Alicia Reyes-Arellano*
Escuela Nacional de Ciencias Biológicas, IPN, Departamento de Química Orgánica,
Carpio y Plan de Ayala S/N, Colonia Santo Tomás, 11340 México, D. F, México
(Received February 15, 2010; CL-100162; E-mail: areyesa@ipn.mx)
A
reductive pinacol type arylaldehyde homocoupling
Table 1. Reductive dimerization of benzaldehyde and substi-
process mediated by the [Cr(en)2]2+ complex is described. This
procedure affords the meso-stereoisomer as the major product,
an unexpected result considering that most organometallic
methodologies preferentially yield the dl-isomer. Additionally,
tuted aromatic aldehydes
OH
OH
1. [Cr(en)
2]Cl2 / DMF
O
Ar
Ar
OH
meso
+
Ar
Ar
Ar
H
2.H
2O
OH
the method represents a novel application of the [Cr(en)2]2+
.
dl
:
2
3
1
Total
Total
yielde
/%f
1,2-diols, dl:meso
yieldc
Reductive pinacol type coupling has been an important
reaction in organic synthesis since its discovery.1 Development
of new improved reagents for synthetic applications of 1,2-diols
constantly appear in the literature, such as a sophisticated
vanadium complex for the cross coupling of aromatic aldehydes2
and an electride which was used in a pinacol coupling reaction
in aqueous medium, giving low to moderate yields.3
Ar
3a
ratiob
/%d
C6H5
p-CH3-C6H4
p-(CH3)2CH-C6H4
p-CH3O-C6H4
p-Br-C6H4
3a
3b
3ch
3d
3ei
3f
2:98
25:75
2:98
78g (74) 98 (96)
57 (42) 98 (73)
33 (30) 94 (88)
36 (32) 78 (73)
53 (38) 70 (50)
42 (32) 98 (78)
65 (45) 96 (73)
2:98
25:75
25:75
25:75
It is worth mentioning that CrCl2 and derived complexes
have resulted in useful reagents for many synthetic trans-
formations, mainly C-C coupling reactions and a large amount
of information is available.4 However diol formation is a side
process when Cr(II) is used during aldehyde alkylation.5 Indeed
we also observed pinacol coupling during alkylation of alde-
hydes with [Cr(en)2]2+/DMF.5c Strategies aimed to obtain the
arylaldehyde dimerization using Cr(II) have involved Zn or Mn
powder, chlorosilanes and a catalytic amount of CrCl2 or CrCl3
and chromium complexes such as Cp2Cr or (BiPy)2Cr. Best
yield was given by benzaldehyde (88%), other arylaldehydes
dimerized in the range 51-77%.6 The reductive pinacol type
aldehyde homocoupling process is mainly made with other
reagents and other transition metals7 and here the SmI2
participation is privileged.8 On the other hand, the [Cr(en)2]2+
complex is an interesting reagent, although it is scarcely used in
organic synthesis. This complex was used in the reduction of ½-
alkenyl halides to afford cyclic products,9 it is also a useful
reagent for the addition of alkyl halides to electron-deficient
alkenes.10
p-CN-C6H4
m-CH3-C6H4
3g
aThe spectroscopic data are in agreement with those reported in
the literature.8a,13,14 bDetermined by 1H NMR spectroscopy.
cYield meso:dl. (Isolated yield meso-isomer), water work up.
d
eYield meso:dl. (Isolated yield meso-isomer), aqueous NH4Cl
f
g
1
work up. 88% yield determined by H NMR using toluene as
internal standard. h3c is a new compound and it was fully
characterized.15 iReaction was carried out at ¹10 °C.
CrCl2 and the [Cr(en)2]2+ complex have participated in
some processes involving radicals: ½-hexenyl bromide reduc-
tion,9 the trapping of radicals by electron-withdrawing substi-
tuted alkenes10 and the tandem carbon-carbon bond reaction.16
On these grounds it is possible to assume that radicals are
involved in the dimerization reaction at hand. In addition, it is
known that sterically crowded radicals predominantly yield
meso-dimers.17 Thus, the complex [Cr(en)2]2+ behaves in a
similar way as SmI2, transferring a single electron during the
reduction process. Experiments are currently in progress to find
out the origin of the meso-selectivity.
Herein, a novel application of the [Cr(en)2]2+ complex in an
alternative method for the synthesis of 1,2-diols via arylaldehyde
dimerization is described.
Benzaldehyde was reductively dimerized to the correspond-
ing 1,2-diol upon treatment with the [Cr(en)2]2+ complex at
room temperature, furnishing the meso-isomer as the main
product (96%) and only traces of the dl-coupling diastereoisom-
er. An unusual result considering that most of pinacol coupling
organometallic mediated processes afford either a 1:1 meso-dl
mixture or the dl-isomer as the major product.6,8,11 Boland
obtained 1,2-diphenyl-1,2-ethanediol as 30:70 dl:meso mixture
with Cp2Cr.6 Very recently high meso-diastereoselectivity in diol
formation from aldehydes was attained using aluminum pow-
der/copper sulfate as catalysts.12
The dimerization obtained with benzaldehyde prompted the
application of the Cr(II) complex on other aromatic aldehydes.
Of particular interest were 4-substituted arylaldehydes, since the
effect of different electron-donating or electron-attracting con-
tributions to the carbonyl moiety could be evaluated. The result
of the reductive process is summarized in Table 1.
It is clear from the table that the [Cr(en)2]2+ complex
reductively dimerized aromatic aldehydes to vic-diols, with the
meso-coupling products being preferentially formed. However,
electronic contributions from the 4-substituents had no impact
on the reaction and consequently no trend was established in the
Chem. Lett. 2010, 39, 500-501
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

501
1,2-diol production. Thus, p-tolualdehyde gave a similar yield of
the 1,2-diol as p-cyanobenzaldehyde, no reduction of the nitrile
group by the complex was observed. It is also notable that
reductive dimerization was not observed with p-nitrobenzalde-
hyde or N,N-dimethylaminobenzaldehyde. With the former the
corresponding nitrobenzyl alcohol was the sole isolated com-
pound. With the latter, no product was isolated, nor was any
starting material recovered. 2-Naphthaldehyde did not react at
all and the starting material was fully recovered. 2,4-Dimethyl-
benzaldehyde and o-tolualdehyde did not undergo the reductive
dimerization process, instead the corresponding alcohol was
isolated, indicating that steric hindrance may be playing an
important role during the process, m-tolualdehyde did produce
the corresponding vicinal diol.
Financial support for this work by CONACYT (Mexico)
through Research Grant No. 90894 and by IPN through
Research Grants Nos. SIP 20090943 and 20100679 is gratefully
acknowledged. A.A.S and R.R.D. are thankful to CONACYT
(Mexico) for a graduate scholarship.
References and Notes
1
2
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diffraction of the supramolecular structures obtained from each
of these diols with imines.
Procedures related to the one herein described include the
diastereoselective and enantioselective dimerization of arylalde-
hydes by TiCl2 in the presence of a variety of enantiopure
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6
7
8
Particularly interesting was a dl-diastereoselective pinacol
coupling with Ti(III),17 which showed that aldehydes with
electron-withdrawing substituents give better dimerization
yields as compared to those substituted with electron donors.
The last procedure is in contrast with the results obtained in the
present investigation. Thus, it seems that several factors
influence the reductive pinacol process,7,20 including the metal
oxidation state, the ligands involved, and the reaction conditions
(i.e., temperature).7,17,21 In our case, experimental procedures are
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Cr(II).10 The effect of temperature on the process and the use of
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factor in the overall yield. Quenching the reaction with water10
gave low to moderate yields, while strong acid conditions were
avoided, as they would have led to a protonated product more
soluble in water. But treatment of the reaction crude with 5%
aqueous NH4Cl solution during 4 h increased the isolation yields
(Table 1).
We consider that the method developed in the current study
is competitive with those already described in the literature, even
with one using aluminum powder/copper sulfate.12 A method-
ology for diastereoselective hydrobenzoin synthesis based on
the use of the [Cr(en)2]2+ complex was developed. This novel
application of the [Cr(en)2]2+ complex predominantly formed
meso-isomers in yields comparable to those obtained with other
organometallic assisted processes. Therefore, this method-
ology represents an alternative for vicinal diol synthesis, with
the advantage that the use of chromium is a simple and
inexpensive protocol. Procedures are available in Supporting
Information.15
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Chem. Lett. 2010, 39, 500-501
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/